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U.S. Environmental Protection Agency
U.S. EPA Technology Innovation and Field Services Division

Per- and Polyfluoroalkyl Substances (PFASs)

Toxicology

This section provides reviews from a variety of sources on the toxicology (human and ecological) of PFASs. The largest amount of information concerns PFOA, PFOS, and their salts and precursors. Individual specific studies are not called out but can be found in the extensive bibliographies of the resources listed. The resources below also include links to publicly available databases that can be searched for information on the toxicology of PFOA, PFOS, and other PFAS compounds.


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Human Health Effects | Ecological Effects | Databases and Websites | Human Health | Ecological Health

Human Health Effects

PFOS

Data on the effects of PFOS in humans and animals demonstrate ready absorption of PFOS and distribution of the chemical throughout the body by noncovalent binding to serum albumin and other plasma proteins. In animal models, PFOS is detected predominantly in liver, serum, and kidney. Studies of postmortem human tissues identify its presence in liver. Both experimental data and pharmacokinetic models show higher levels of PFOS in fetal serum and brain compared with the maternal compartments. PFOS is not readily eliminated from humans as evidenced by the estimated average half-life values of 4.1-8.67 years (USEPA 2016a).

Because of uncertainties associated with the human data, EPA is currently relying on animal data to quantitatively assess effects; however, the epidemiology studies provide important data to establish probable links between PFOS exposure to humans and health effects. In particular, effects on the liver enzymes indicative of liver effects, low birth weight, antibody response, and cancer in laboratory animals are supported by human epidemiology studies coupled with PBPK modeling to extrapolate to humans (USEPA 2016b).

PFOA

Extensive data on the effects of PFOA in humans and animals indicate ready absorption of PFOA and distribution of the chemical throughout the body by noncovalent binding to plasma proteins. In the mouse, PFOA is detected predominantly in liver, serum, and kidney. Studies of postmortem human tissues identify its presence in liver, lung, kidney, and bone. PFOA is not readily eliminated from the human body as evidenced by the half-life of 2.3 years among members of the general population (EPA 2016c).

Human epidemiology data report associations between PFOA exposure and high cholesterol, increased liver enzymes, decreased vaccination response, thyroid disorders, pregnancy-induced hypertension and preeclampsia, and cancer (testicular and kidney) (EPA 2016d).

Because of uncertainties associated with the human data, EPA is currently relying on animal data to quantitatively assess effects; however, the epidemiology studies provide important data to establish probable links between PFOA exposure to humans and health effects. In particular, effects on the liver enzymes indicative of liver effects, low birthweight, immunological (acquired and innate) responses, and tumor induction in laboratory animals are supported by human epidemiology studies and PBPK modeling (USEPA 2016d).

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Ecological Effects

Environmental toxicity tends to be chemical and species specific and hence is not easily summarized. Giesy et al. (2010) states: "Results available in the literature on the toxicity of PFCs to aquatic organisms indicate that toxicity of fluorinated chemicals is related to length of the fluorinated carbon chain; the nature of functional groups has relatively little effect on the toxic potency of these compounds." A summary of some older studies on PFOS effects on selected plants and animals can be found in OECD (2002). The overview documents in the Ecological Health section generally contain extensive reference lists relevant to ecological effects.

References

Giesy, J., J. Naile, J.S. Khim, P. Jones, and J. Newsted. 2010. Aquatic toxicology of perfluorinated chemicals.Adobe PDF Logo Reviews of Environmental Contamination and Toxicology 202:1-52.

OECD (Organisation for Economic Co-operation and Development). 2002. Hazard Assessment of Perfluorooctane Sulfonate (PFOS) and Its Salts.Adobe PDF Logo Environment Directorate, 362 pp.

USEPA (U.S. Environmental Protection Agency). 2016a. Health Effects Support Document for Perfluorooctane Sulfonate (PFOS).Adobe PDF Logo Office of Water. EPA 822 R-16-002, 245 pp.

USEPA (U.S. Environmental Protection Agency). 2016b. Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS).Adobe PDF Logo Office of Water. EPA 822-R-16-004, 88 pp.

USEPA (U.S. Environmental Protection Agency). 2016c. Health Effects Support Document for Perfluorooctanic Acid (PFOA).Adobe PDF Logo Office of Water. EPA 822 R-16-003, 322 pp.

USEPA (U.S. Environmental Protection Agency). 2016d. Drinking Water Health Advisory for Perfluorooctanoic Acid (PFOA).Adobe PDF Logo Office of Water. EPA 822-R-16-005, 103 pp.

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Databases and Websites

The C8 Science Panel Website
During 2005-2013, the C8 Science Panel carried out exposure and health studies in Mid-Ohio Valley communities potentially affected by releases of PFOA (i.e., C8) emitted since the 1950s from the Washington Works plant in Parkersburg, West Virginia. The investigators then assessed the links between C8 exposure and a number of diseases. The C8 Science Panel has completed its work and no longer exists; results are summarized on this website.

ECOTOX
The U.S. EPA ECOTOXicology knowledgebase (ECOTOX) is a comprehensive, publicly available database that provides single-chemical environmental toxicity data on aquatic life, terrestrial plants, and wildlife.

HERO
EPA's Health and Environmental Research Online (HERO) database contains more than 600,000 scientific references and data from the peer-reviewed literature used by EPA to develop its regulations. The assessments supported by HERO characterize the nature and magnitude of health risks to humans and the ecosystem from pollutants and chemicals in the environment. HERO is an evergreen database, which means that new studies are added continuously. Imported references are systematically sorted, classified, and made available for search and citation.

PubMed
PubMed comprises tens of millions of citations for literature from MEDLINE, life science journals, and online books in the fields of biomedicine and health, covering portions of the life sciences, behavioral sciences, chemical sciences, and bioengineering. PubMed is a free resource developed and maintained by the National Center for Biotechnology Information at the National Library of Medicine®.

TOXNET
TOXNET is a gateway to a variety of databases, including HSDB, the Hazardous Substances Data Bank, which offers peer-reviewed toxicology data for over 5,000 hazardous chemicals, and TOXLINE, which contains 4 million references to literature on biochemical, pharmacological, physiological, and toxicological effects of drugs and other chemicals.

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Human Health

A Critical Review of Perfluorooctanoate and Perfluorooctanesulfonate Exposure and Cancer Risk in Humans
Chang, E.T., H.-O. Adami, P. Boffetta, P. Cole, T.B. Starr, and J.S. Mandel.
Critical Reviews in Toxicology 44(sup1):1-81(2014)

This Open Access journal article contains a detailed review of epidemiologic evidence concerning the association between PFOA and PFOS exposure and cancer risk in humans.

Adobe PDF LogoDrinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS)
U.S. EPA, Office of Water.
EPA 822-R-16-004, 88 pp, 2016

EPA issued a lifetime drinking water health advisory for PFOS of 0.07 µg/L based on review of recent health effects information as described in EPA's 2016 Health Effects Support Document for Perfluorooctane Sulfonate (PFOS).

Adobe PDF LogoDrinking Water Health Advisory for Perfluorooctanic Acid (PFOA)
U.S. EPA, Office of Water.
EPA 822-R-16-005, 103 pp, 2016

EPA issued a lifetime drinking water Health Advisory for PFOA of 0.07 µg/L based on review of recent health effects information described in EPA's 2016 Health Effects Support Document for Perfluorooctanoic Acid (PFOA).

Adobe PDF LogoEnvironmental and Health Risk Assessment of Perfluoroalkylated and Polyfluoroalkylated Substances (PFASs) in Sweden
Borg, D. and H. Hakanson.
Swedish Environmental Protection Agency, Report 6513, 139 pp, 2012

The risk assessment consisted of (1) an exposure assessment with Swedish biomonitoring data for 23 PFASs measured in humans, mammals, birds, and fish; (2) a hazard assessment with toxicological data from studies on mammals, birds, and fish for the selected compounds; and (3) a risk characterization for humans, mammals, birds, and fish. The investigators reviewed a large number of PFASs individually and in combination.

Adobe PDF LogoHazard Assessment of Perfluorooctane Sulfonate (PFOS) and Its Salts
OECD (Organisation for Economic Co-operation and Development), Environment Directorate.
ENV/JM/RD(2002)17/FINAL, 362 pp, 2002

Separate sections of this overview cover physical-chemical properties, environmental behavior and fate, human health hazards, and hazards to the environment (fish, invertebrates, aquatic plants, and terrestrial organisms and plants).

Adobe PDF LogoHealth Effects Support Document for Perfluorooctane Sulfonate (PFOS)
U.S. EPA, Office of Water.
EPA 822-R-16-002, 245 pp, 2016

Information is provided on PFOS toxicokinetics, hazard identification (human effects, animal studies, and hazard characterization), and dose-response assessment.

Adobe PDF LogoHealth Effects Support Document for Perfluorooctanic Acid (PFOA)
U.S. EPA, Office of Water.
EPA 822-R-16-003, 322 pp, 2016

This document covers PFOA toxicokinetics, hazard identification (human effects, animal studies, and hazard characterization), and dose-response assessment.

Adobe PDF LogoProvisional Peer Reviewed Toxicity Values for Perfluorobutane Sulfonate and Related Compound Potassium Perfluorobutane Sulfonate
U.S. EPA, Office of Research and Development, 50 pp, 2014

Provisional Peer-Reviewed Toxicity Values (PPRTVs) are second-tier human health toxicity values for the EPA Superfund and RCRA hazardous waste programs.

Adobe PDF LogoScreening Assessment Report: Perfluorooctanoic Acid, Its Salts, and Its Precursors
Environment Canada and Health Canada, 97 pp, 2012

The assessment is based on a weight-of-evidence approach regarding the persistence, bioaccumulation, temporal trends in some species (e.g., the polar bear), long-range transport, and the widespread occurrence and concentrations of PFOA in the environment and biota (including remote areas of Canada). The report discusses ecological risk assessment and human health risk assessment with supporting data and 26 pages of bibliographic references.

Adobe PDF LogoShort-Chain Polyfluoroalkyl Substances (PFAS): A Literature Review of Information on Human Health Effects and Environmental Fate and Effect Aspects of Short-Chain PFAS
Danish Ministry of the Environment, Environmental Protection Agency. Environmental project No. 1707, 106 pp, 2015

The literature review was conducted to provide an overview of the human health and environmental fate and effects aspects of short-chain polyfluorinated substances introduced as alternatives to PFOS, PFOA, and other long-chain PFASs.

Toxicology of Perfluorinated Compounds
Stahl, T., D. Mattern, and H. Brunn.
Environmental Sciences Europe 23(38):1-52(2011)

This Open Access journal article describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity [carcinogenesis, genotoxicity, and epigenetic effects], reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies).

Ecological Health

Adobe PDF LogoAquatic Toxicology of Perfluorinated Chemicals
Giesy, J., J. Naile, J.S. Khim, P. Jones, and J. Newsted.
Springer Science. Reviews of Environmental Contamination and Toxicology 202:1-52(2010)
DOI: 10.1007/978-1-4419-1157-5_1

Following a general discussion of PFC fate in the environment, specific acute and chronic toxicity of PFOS in aquatic organisms is discussed along with the derivation of PFOS and PFBS toxicity reference values for predatory birds.

Environmental Risk Evaluation Report: Perfluorooctanesulphonate (PFOS)
Brooke, D., A. Footitt, and T. Nwaogu.
Environment Agency, United Kingdom, SCHO1009BRBL-E-P, 104 pp, 2004

Potential exposure pathways in the environment via the major uses for PFOS-related substances are described, followed by a review of toxicity information relevant to aquatic organisms and subsequent effects on the ecological food chain.

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